CORE A SUMMARY/ABSTRACT Our proposed U54 Center application entitled Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood Cancers is a multi-disciplinary and multi-institutional effort that we think is directly responsive to the RFAs designed to create the Pediatric Immunotherapy Discovery and Development Network (PI-DDN). Built on years of multi-disciplinary collaboration amongst Project and Core Principal Investigators and their research teams, we plan to directly address critical unmet needs uniquely relevant to children with high-risk cancers. To accomplish our Center goals, we propose experienced leadership to define priorities, sustain momentum and deliver results that meet defined milestones on time and under budget. The proposed co-PIs Drs. Maris and Mackall have worked together to lead complex research programs and coordinate integrated and collaborative experimentation. Here, we propose an administrative Core that will provide the scientific, statistical and administrative leadership to achieve the mission of the proposed investigation. With experienced statistical and administrative support, we will organize the recurring meetings and day-to-day operation of the Center and interactions with the PI-DDN and other immunotherapy efforts. The Core will support the scientific interchange necessary for the ambitious scientific goals of each Project and the Center as a whole, encourage input from pediatric cancer advocates to help shape our mission, oversee the allocation of budget on a quarterly basis as our research evolves, assure regulatory compliance, and promote experimental rigor and transparency.